Cancer is a fatal disease accounting for a large percentage of the causes of death in humans. Currently, the ratio of cancer to the causes of death is still tending to rise. Available methods of its treatment include surgical therapy, radiotherapy, chemotherapy and the like. In addition to these therapies, there have been developed inhibitors that target molecules that are highly expressed specifically in cancer cells and promote cell proliferation, and what is called molecular targeted therapy is implemented. However, search for new molecular targets and ensuing drug discovery still represents the most important research objects.
The present inventors searched for genes whose expression is induced by DNA damage signals by the differential display method. As a result, the present inventors identified the transcription factor ZNF143. This gene was isolated and identified as a transcription factor of the selenocysteine tRNA gene from the African clawed frog in 1995 (Non-patent document 1). Later, a functional analysis thereof as a transcription factor was announced. The present inventors reported that the expression of ZNF143 is induced at the transcriptional level by anticancer agents and gamma rays, which cause DNA damage, and that ZNF143 recognizes cisplatin-bridged DNA (Non-patent document 2). Furthermore, the present inventors found that ZNF143 is highly expressed in cisplatin-resistant cancer cells, that the cells become sensitive to cisplatin when the expression of ZNF143 is suppressed, and that ZNF143 positively controls the expression of many DNA repair gene groups (Non-patent document 3).
Results of a genome-wide search for sequences that bind to the ZNF143 polypeptide have been reported so far (Non-patent document 4). The report concerns analytical results for genome information and represents nothing more than the finding of a broad range of different genes associated with ZNF143. The report does not analyze what functions are possessed by the broad range of genes at all.
Meanwhile, mechanisms for cancer cell proliferation are being elucidated at the molecular level. In particular, molecules that influence the cell cycle are attracting attention as preferred molecular targets for cancer treatment.
Regarding the cell cycle, a brief explanation is given here. The cell cycle consists of four processes; the individual processes are called the G1 phase, S phase (DNA replication phase), G2 phase, and M phase (division phase), arranged in time sequence. At the ends of the G1 phase and G2 phase (the latter also referred to as the G2/M phase), a surveillance mechanism for sensing DNA abnormalities works, and this mechanism is called a checkpoint. If a DNA abnormality is repairable by a DNA repair mechanism, the cell cycle proceeds as the DNA abnormality is repaired. If the DNA abnormality is unrepairable, cell death is induced, disenabling the survival of the abnormal cells.
In normal cells, DNA replication proceeds accurately, so it is thought that abnormalities are sensed by making use of the G1 phase checkpoint before the S phase, while the G2 phase checkpoint is hardly utilized. Meanwhile, in the majority of cancer cells, the G1 phase checkpoint is disordered and fails to function, and the G2 phase checkpoint is in an activated state instead. Therefore, to prevent DNA abnormalities from being repaired to cause cell death by inhibiting the G2 phase checkpoint in cancer cells is the most purposeful for a therapeutic drug for cancer. Furthermore, such therapeutic drugs seem to have less influence on normal cells.    Non-patent document 1: Schuster C. et al. EMBO J. 1995, 14, p3777-3787    Non-patent document 2: Ishiguchi H. et al. Int. J. Cancer 2004, 111, p900-909    Non-patent document 3: Wakasugi T. et al. Oncogene 2007 26, p5194-5203    Non-patent document 4: Myslinski E. et al. J. Biol Chem 2006 281, p39953-39963